NPC1_MOUSE
ID NPC1_MOUSE Reviewed; 1277 AA.
AC O35604; G3X8W9; O35605;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 06-FEB-2013, sequence version 2.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=NPC intracellular cholesterol transporter 1 {ECO:0000312|MGI:MGI:1097712};
DE AltName: Full=Niemann-Pick C1 protein {ECO:0000303|PubMed:9211850};
DE Flags: Precursor;
GN Name=Npc1 {ECO:0000312|MGI:MGI:1097712};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], TISSUE SPECIFICITY, AND DISEASE.
RX PubMed=9211850; DOI=10.1126/science.277.5323.232;
RA Loftus S.K., Morris J.A., Carstea E.D., Gu J.Z., Cummings C., Brown A.,
RA Ellison J., Ohno K., Rosenfeld M.A., Tagle D.A., Pentchev P.G., Pavan W.J.;
RT "Murine model of Niemann-Pick C disease: mutation in a cholesterol
RT homeostasis gene.";
RL Science 277:232-235(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Heart, Kidney, Liver, Lung, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=16340014; DOI=10.1194/jlr.m500482-jlr200;
RA Karten B., Campenot R.B., Vance D.E., Vance J.E.;
RT "The Niemann-Pick C1 protein in recycling endosomes of presynaptic nerve
RT terminals.";
RL J. Lipid Res. 47:504-514(2006).
RN [6]
RP REVIEW ON FUNCTION.
RX PubMed=21412152; DOI=10.1097/mol.0b013e3283453e69;
RA Vance J.E., Peake K.B.;
RT "Function of the Niemann-Pick type C proteins and their bypass by
RT cyclodextrin.";
RL Curr. Opin. Lipidol. 22:204-209(2011).
RN [7]
RP INTERACTION WITH NPC2, SUBCELLULAR LOCATION, GLYCOSYLATION, AND MUTAGENESIS
RP OF VAL-378; ARG-404 AND ARG-518.
RX PubMed=22065762; DOI=10.1073/pnas.1110439108;
RA Deffieu M.S., Pfeffer S.R.;
RT "Niemann-Pick type C 1 function requires lumenal domain residues that
RT mediate cholesterol-dependent NPC2 binding.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:18932-18936(2011).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, GLYCOSYLATION, AND
RP MUTAGENESIS OF 202-PRO-PHE-203.
RX PubMed=21896731; DOI=10.1073/pnas.1112751108;
RA Xie X., Brown M.S., Shelton J.M., Richardson J.A., Goldstein J.L.,
RA Liang G.;
RT "Amino acid substitution in NPC1 that abolishes cholesterol binding
RT reproduces phenotype of complete NPC1 deficiency in mice.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:15330-15335(2011).
RN [9]
RP FUNCTION, DISEASE, TISSUE SPECIFICITY, AND MUTAGENESIS OF ASP-1005.
RX PubMed=22048958; DOI=10.1093/hmg/ddr505;
RA Maue R.A., Burgess R.W., Wang B., Wooley C.M., Seburn K.L., Vanier M.T.,
RA Rogers M.A., Chang C.C., Chang T.Y., Harris B.T., Graber D.J.,
RA Penatti C.A., Porter D.M., Szwergold B.S., Henderson L.P., Totenhagen J.W.,
RA Trouard T.P., Borbon I.A., Erickson R.P.;
RT "A novel mouse model of Niemann-Pick type C disease carrying a D1005G-Npc1
RT mutation comparable to commonly observed human mutations.";
RL Hum. Mol. Genet. 21:730-750(2012).
RN [10]
RP FUNCTION, INTERACTION WITH NPC2, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP GLU-421; 502-ASP--TYR-504 AND 503-PHE-TYR-504.
RX PubMed=27551080; DOI=10.1073/pnas.1611956113;
RA Li X., Saha P., Li J., Blobel G., Pfeffer S.R.;
RT "Clues to the mechanism of cholesterol transfer from the structure of NPC1
RT middle lumenal domain bound to NPC2.";
RL Proc. Natl. Acad. Sci. U.S.A. 113:10079-10084(2016).
CC -!- FUNCTION: Intracellular cholesterol transporter which acts in concert
CC with NPC2 and plays an important role in the egress of cholesterol from
CC the endosomal/lysosomal compartment (PubMed:21896731, PubMed:22048958,
CC PubMed:27551080). Unesterified cholesterol that has been released from
CC LDLs in the lumen of the late endosomes/lysosomes is transferred by
CC NPC2 to the cholesterol-binding pocket in the N-terminal domain of
CC NPC1. Cholesterol binds to NPC1 with the hydroxyl group buried in the
CC binding pocket (By similarity). May play a role in vesicular
CC trafficking in glia, a process that may be crucial for maintaining the
CC structural and functional integrity of nerve terminals (Probable).
CC {ECO:0000250|UniProtKB:O15118, ECO:0000269|PubMed:21896731,
CC ECO:0000269|PubMed:22048958, ECO:0000269|PubMed:27551080, ECO:0000305}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=cholesterol(in) = cholesterol(out); Xref=Rhea:RHEA:39747,
CC ChEBI:CHEBI:16113; Evidence={ECO:0000250|UniProtKB:O15118};
CC -!- SUBUNIT: Interacts (via the second lumenal domain) with NPC2
CC (PubMed:22065762, PubMed:27551080). Interacts with TMEM97. Interacts
CC with TIM1 (By similarity). {ECO:0000250|UniProtKB:O15118,
CC ECO:0000269|PubMed:22065762, ECO:0000269|PubMed:27551080}.
CC -!- INTERACTION:
CC O35604; A0A0F6B1Q8: sseJ; Xeno; NbExp=3; IntAct=EBI-13641434, EBI-10760263;
CC -!- SUBCELLULAR LOCATION: Late endosome membrane
CC {ECO:0000250|UniProtKB:O15118}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:O15118}. Lysosome membrane
CC {ECO:0000269|PubMed:21896731, ECO:0000269|PubMed:22065762,
CC ECO:0000269|PubMed:27551080}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:O15118}.
CC -!- TISSUE SPECIFICITY: Detected in liver (at protein level)
CC (PubMed:21896731, PubMed:22048958). Ubiquitous (PubMed:9211850).
CC Detected in adult heart, spleen, lung, liver, skeletal muscle, kidney,
CC testis (PubMed:9211850). {ECO:0000269|PubMed:21896731,
CC ECO:0000269|PubMed:22048958, ECO:0000269|PubMed:9211850}.
CC -!- DOMAIN: A cysteine-rich N-terminal domain and a C-terminal domain
CC containing a di-leucine motif necessary for lysosomal targeting are
CC critical for mobilization of cholesterol from lysosomes.
CC {ECO:0000250|UniProtKB:O15118}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:21896731,
CC ECO:0000269|PubMed:22065762}.
CC -!- DISEASE: Note=Defects in Npc1 cause a lysosomal storage disorder
CC characterized by accumulation of cholesterol in lysosomes and impaired
CC cholesterol homeostasis. Causes age-dependent loss of Purkinje cells,
CC loss of body weight and leads then to ataxia and premature death at a
CC median age of 72 days. {ECO:0000269|PubMed:22048958,
CC ECO:0000269|PubMed:9211850}.
CC -!- SIMILARITY: Belongs to the patched family. {ECO:0000305}.
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DR EMBL; AF003348; AAB63372.1; -; mRNA.
DR EMBL; AF003349; AAB63373.1; -; Genomic_DNA.
DR EMBL; AC102096; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC102248; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466622; EDL01560.1; -; Genomic_DNA.
DR CCDS; CCDS29064.1; -.
DR PIR; T30188; T30188.
DR RefSeq; NP_032746.2; NM_008720.2.
DR AlphaFoldDB; O35604; -.
DR SMR; O35604; -.
DR BioGRID; 201820; 13.
DR IntAct; O35604; 1.
DR MINT; O35604; -.
DR STRING; 10090.ENSMUSP00000025279; -.
DR ChEMBL; CHEMBL2321610; -.
DR SwissLipids; SLP:000000479; -.
DR GlyConnect; 2563; 2 N-Linked glycans (2 sites).
DR GlyGen; O35604; 16 sites, 2 N-linked glycans (2 sites).
DR iPTMnet; O35604; -.
DR PhosphoSitePlus; O35604; -.
DR SwissPalm; O35604; -.
DR EPD; O35604; -.
DR jPOST; O35604; -.
DR MaxQB; O35604; -.
DR PaxDb; O35604; -.
DR PeptideAtlas; O35604; -.
DR PRIDE; O35604; -.
DR ProteomicsDB; 295510; -.
DR Antibodypedia; 7463; 418 antibodies from 39 providers.
DR DNASU; 18145; -.
DR Ensembl; ENSMUST00000025279; ENSMUSP00000025279; ENSMUSG00000024413.
DR GeneID; 18145; -.
DR KEGG; mmu:18145; -.
DR UCSC; uc008ecb.1; mouse.
DR CTD; 4864; -.
DR MGI; MGI:1097712; Npc1.
DR VEuPathDB; HostDB:ENSMUSG00000024413; -.
DR eggNOG; KOG1933; Eukaryota.
DR GeneTree; ENSGT00940000156182; -.
DR HOGENOM; CLU_002359_0_0_1; -.
DR InParanoid; O35604; -.
DR OMA; CPDNGLA; -.
DR OrthoDB; 731120at2759; -.
DR PhylomeDB; O35604; -.
DR TreeFam; TF300416; -.
DR Reactome; R-MMU-8964038; LDL clearance.
DR BioGRID-ORCS; 18145; 4 hits in 79 CRISPR screens.
DR ChiTaRS; Npc1; mouse.
DR PRO; PR:O35604; -.
DR Proteomes; UP000000589; Chromosome 18.
DR RNAct; O35604; protein.
DR Bgee; ENSMUSG00000024413; Expressed in secondary oocyte and 251 other tissues.
DR Genevisible; O35604; MM.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0005768; C:endosome; IDA:MGI.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IDA:MGI.
DR GO; GO:1905103; C:integral component of lysosomal membrane; ISS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0031902; C:late endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005764; C:lysosome; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0045121; C:membrane raft; IDA:MGI.
DR GO; GO:0005635; C:nuclear envelope; IDA:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:0031982; C:vesicle; IDA:MGI.
DR GO; GO:0015485; F:cholesterol binding; ISS:UniProtKB.
DR GO; GO:0005319; F:lipid transporter activity; IEA:InterPro.
DR GO; GO:0032934; F:sterol binding; IBA:GO_Central.
DR GO; GO:0007628; P:adult walking behavior; IGI:MGI.
DR GO; GO:0006914; P:autophagy; ISO:MGI.
DR GO; GO:0008206; P:bile acid metabolic process; ISS:UniProtKB.
DR GO; GO:0071404; P:cellular response to low-density lipoprotein particle stimulus; IDA:MGI.
DR GO; GO:0071383; P:cellular response to steroid hormone stimulus; IDA:MGI.
DR GO; GO:0033344; P:cholesterol efflux; IMP:MGI.
DR GO; GO:0042632; P:cholesterol homeostasis; IMP:UniProtKB.
DR GO; GO:0008203; P:cholesterol metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0030301; P:cholesterol transport; ISS:UniProtKB.
DR GO; GO:0006897; P:endocytosis; IMP:MGI.
DR GO; GO:0051649; P:establishment of localization in cell; IMP:MGI.
DR GO; GO:0090150; P:establishment of protein localization to membrane; ISO:MGI.
DR GO; GO:0010467; P:gene expression; IMP:MGI.
DR GO; GO:0030299; P:intestinal cholesterol absorption; IBA:GO_Central.
DR GO; GO:0032367; P:intracellular cholesterol transport; ISS:UniProtKB.
DR GO; GO:0007041; P:lysosomal transport; ISS:UniProtKB.
DR GO; GO:0016236; P:macroautophagy; IMP:MGI.
DR GO; GO:0031579; P:membrane raft organization; ISO:MGI.
DR GO; GO:0060548; P:negative regulation of cell death; ISO:MGI.
DR GO; GO:0016242; P:negative regulation of macroautophagy; IMP:MGI.
DR GO; GO:0006486; P:protein glycosylation; IDA:UniProtKB.
DR GO; GO:0046686; P:response to cadmium ion; ISO:MGI.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IDA:MGI.
DR GO; GO:0015918; P:sterol transport; IBA:GO_Central.
DR GO; GO:0046718; P:viral entry into host cell; IMP:CACAO.
DR InterPro; IPR004765; NPC1-like.
DR InterPro; IPR032190; NPC1_N.
DR InterPro; IPR003392; Ptc/Disp.
DR InterPro; IPR000731; SSD.
DR Pfam; PF16414; NPC1_N; 1.
DR Pfam; PF02460; Patched; 1.
DR Pfam; PF12349; Sterol-sensing; 1.
DR TIGRFAMs; TIGR00917; 2A060601; 1.
DR PROSITE; PS50156; SSD; 1.
PE 1: Evidence at protein level;
KW Cholesterol metabolism; Disulfide bond; Endosome; Glycoprotein;
KW Lipid metabolism; Lipid transport; Lysosome; Membrane; Reference proteome;
KW Signal; Steroid metabolism; Sterol metabolism; Transmembrane;
KW Transmembrane helix; Transport.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..1277
FT /note="NPC intracellular cholesterol transporter 1"
FT /id="PRO_0000023262"
FT TOPO_DOM 23..269
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 270..290
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 291..350
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 351..371
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 372..621
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 622..642
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 643..653
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 654..674
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 675..683
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 684..704
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 705..730
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 731..751
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 752..759
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 760..780
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 781..832
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 833..853
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 854..1097
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 1098..1118
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1119..1123
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1124..1144
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1145
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 1146..1166
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1167..1194
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1195..1215
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1216..1226
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 1227..1247
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1248..1277
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT DOMAIN 620..785
FT /note="SSD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00199"
FT REGION 175..205
FT /note="Important for cholesterol binding and cholesterol
FT transfer from NPC1 to liposomes"
FT /evidence="ECO:0000250"
FT REGION 1274..1277
FT /note="Required for location in lysosomes"
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT MOTIF 1274..1277
FT /note="Di-leucine motif"
FT /evidence="ECO:0000305"
FT BINDING 41
FT /ligand="cholesterol"
FT /ligand_id="ChEBI:CHEBI:16113"
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT BINDING 79
FT /ligand="cholesterol"
FT /ligand_id="ChEBI:CHEBI:16113"
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT SITE 108
FT /note="Important for cholesterol binding"
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT CARBOHYD 70
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 122
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 137
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 185
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 222
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 228
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 414
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 459
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 478
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 524
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 868
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 898
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 916
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 961
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 968
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1063
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 25..74
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT DISULFID 31..42
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT DISULFID 63..109
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT DISULFID 75..113
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT DISULFID 97..238
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT DISULFID 100..160
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT DISULFID 177..184
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT DISULFID 227..243
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT DISULFID 240..247
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT DISULFID 468..479
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT DISULFID 516..533
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT DISULFID 909..914
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT DISULFID 956..1011
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT DISULFID 957..979
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT DISULFID 967..976
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT MUTAGEN 202..203
FT /note="PF->AA: Loss of function giving rise to cholesterol
FT accumulation in kidney, liver, lung and spleen. No effect
FT on lysosomal location. Mice display age-dependent weight
FT loss, neurodegeneration with loss of Purkinje cells, ataxia
FT and premature death at a median age of 84 days."
FT /evidence="ECO:0000269|PubMed:21896731"
FT MUTAGEN 378
FT /note="V->A: No effect on affinity for NPC2."
FT /evidence="ECO:0000269|PubMed:22065762"
FT MUTAGEN 404
FT /note="R->Q: Decreased affinity for NPC2."
FT /evidence="ECO:0000269|PubMed:22065762"
FT MUTAGEN 421
FT /note="E->A: Strongly decreased affinity for NPC2; when
FT associated with 503-A-A-504."
FT /evidence="ECO:0000269|PubMed:27551080"
FT MUTAGEN 502..504
FT /note="DFY->AAA: Strongly decreased affinity for NPC2."
FT /evidence="ECO:0000269|PubMed:27551080"
FT MUTAGEN 503..504
FT /note="FY->AA: Decreased affinity for NPC2. Loss of
FT function in cholesterol transport. No effect on subcellular
FT location. Strongly decreased affinity for NPC2; when
FT associated with A-421."
FT /evidence="ECO:0000269|PubMed:27551080"
FT MUTAGEN 518
FT /note="R->Q: Strongly decreased affinity for NPC2. No
FT effect on lysosomal location."
FT /evidence="ECO:0000269|PubMed:22065762"
FT MUTAGEN 1005
FT /note="D->G: In Npc1-nmf164; strongly decreased protein
FT levels. Causes abnormal lipid storage in the spleen and
FT liver, loss of cerebellar Purkinje cells and age-dependent
FT ataxia."
FT /evidence="ECO:0000269|PubMed:22048958"
FT CONFLICT 9
FT /note="G -> GL (in Ref. 1; AAB63372)"
FT /evidence="ECO:0000305"
FT CONFLICT 135
FT /note="Q -> P (in Ref. 1; AAB63372)"
FT /evidence="ECO:0000305"
FT CONFLICT 147
FT /note="F -> Y (in Ref. 1; AAB63372)"
FT /evidence="ECO:0000305"
FT CONFLICT 445
FT /note="D -> N (in Ref. 1; AAB63372)"
FT /evidence="ECO:0000305"
FT CONFLICT 478
FT /note="N -> D (in Ref. 1; AAB63373)"
FT /evidence="ECO:0000305"
FT CONFLICT 874..875
FT /note="DY -> AN (in Ref. 1; AAB63372)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1277 AA; 142885 MW; 3B42230AAC86764E CRC64;
MGAHHPALGL LLLLLCPAQV FSQSCVWYGE CGIATGDKRY NCKYSGPPKP LPKDGYDLVQ
ELCPGLFFDN VSLCCDIQQL QTLKSNLQLP LQFLSRCPSC FYNLMTLFCE LTCSPHQSQF
LNVTATEDYF DPKTQENKTN VKELEYFVGQ SFANAMYNAC RDVEAPSSNE KALGLLCGRD
ARACNATNWI EYMFNKDNGQ APFTIIPVFS DLSILGMEPM RNATKGCNES VDEVTGPCSC
QDCSIVCGPK PQPPPPPMPW RIWGLDAMYV IMWVTYVAFL FVFFGALLAV WCHRRRYFVS
EYTPIDSNIA FSVNSSDKGE ASCCDPLGAA FDDCLRRMFT KWGAFCVRNP TCIIFFSLAF
ITVCSSGLVF VQVTTNPVEL WSAPHSQARL EKEYFDKHFG PFFRTEQLII QAPNTSVHIY
EPYPAGADVP FGPPLNKEIL HQVLDLQIAI ESITASYNNE TVTLQDICVA PLSPYNKNCT
IMSVLNYFQN SHAVLDSQVG DDFYIYADYH THFLYCVRAP ASLNDTSLLH GPCLGTFGGP
VFPWLVLGGY DDQNYNNATA LVITFPVNNY YNDTERLQRA WAWEKEFISF VKNYKNPNLT
ISFTAERSIE DELNRESNSD VFTVIISYVV MFLYISLALG HIQSCSRLLV DSKISLGIAG
ILIVLSSVAC SLGIFSYMGM PLTLIVIEVI PFLVLAVGVD NIFILVQTYQ RDERLQEETL
DQQLGRILGE VAPTMFLSSF SETSAFFFGA LSSMPAVHTF SLFAGMAVLI DFLLQITCFV
SLLGLDIKRQ EKNHLDILCC VRGADDGQGS HASESYLFRF FKNYFAPLLL KDWLRPIVVA
VFVGVLSFSV AVVNKVDIGL DQSLSMPNDS YVIDYFKSLA QYLHSGPPVY FVLEEGYNYS
SRKGQNMVCG GMGCDNDSLV QQIFNAAELD TYTRVGFAPS SWIDDYFDWV SPQSSCCRLY
NVTHQFCNAS VMDPTCVRCR PLTPEGKQRP QGKEFMKFLP MFLSDNPNPK CGKGGHAAYG
SAVNIVGDDT YIGATYFMTY HTILKTSADY TDAMKKARLI ASNITETMRS KGSDYRVFPY
SVFYVFYEQY LTIIDDTIFN LSVSLGSIFL VTLVVLGCEL WSAVIMCITI AMILVNMFGV
MWLWGISLNA VSLVNLVMSC GISVEFCSHI TRAFTMSTKG SRVSRAEEAL AHMGSSVFSG
ITLTKFGGIV VLAFAKSQIF EIFYFRMYLA MVLLGATHGL IFLPVLLSYI GPSVNKAKRH
TTYERYRGTE RERLLNF
